Dose Finding, Safety and Efficacy of Monthly Subcutaneous Canakinumab Administration for the Treatment of Hyperglycemia in Metformin Monotherapy Treated Type 2 Diabetic Patients: a Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2009-009889-13-BE
• Date of registration: 30/04/2009
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Dose Finding, Safety and Efficacy of Monthly Subcutaneous Canakinumab Administration for the Treatment of Hyperglycemia in Metformin Monotherapy Treated Type 2 Diabetic Patients: a Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study
• Scientific title: Dose Finding, Safety and Efficacy of Monthly Subcutaneous Canakinumab Administration for the Treatment of Hyperglycemia in Metformin Monotherapy Treated Type 2 Diabetic Patients: a Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study
• Date of first enrolment: 25/05/2009
• Target sample size: 600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-009889-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: yes Other trial design description: double-dummy If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Belgium, Germany, Hungary, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients must give written informed consent before any study related procedures are performed.
2. Patients must have a documented diagnosis of Type 2 diabetes confirmed by WHO criteria either a FPG= 7.0 mmol/l (126 mg/dl) or an OGTT test 2-hour PG = 11.1 mmol/l (200 mg/dl). tHis documented diagnosis must be available prior to screening of the patient.
3. Patients must:
• be naïve to anti-diabetes drug therapy (except for short term treatment courses with insulin in connection with hospitalization, etc.)
• have an HbA1c between 7.5% and 11% (inclusive) at Screening analyzed by the Central Laboratory
• be eligible for metformin monotherapy
OR
• be on stable metformin monotherapy treatment for at least three months at Screening
• have an HbA1c between 7.0% and 9% (inclusive) at Screening analyzed by the Central Laboratory
• take metformin as their first and only treatment with anti-diabetes drug therapy (except for short term treatment courses with insulin in connection with hospitalization, etc.)
OR
• be taking an a-glucosidase inhibitor as their first and only treatment with antidiabetes drug therapy (except for short term treatment with insulin in connection with hospitalization, etc)
• have the a-glucosidase inhibitor stopped and be washed out from the a-glucosidase inhibitor for at least a week prior to Run-in.
• have an HbAlc bteween 7% & 9% (inclusive) at screening analyzed by the Central Laboratory.
• be eligible for metformin monotherapy
4. Patients must have a morning fasting plasma glucose result < 180 mg/dl at Visit 3 (Month -1) analyzed by the Central Laboratory.
5. At the Randomization Visit (Month 0), patients must be on a daily dose of metformin = 1000 mg (or less if local regulation does not permit 1000 mg/day).
6. Age from 18-74 years, inclusive, and of either sex.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Type 1 diabetes, diabetes that is teh result of pancreatic injury oer secondary forms of diabetes, e.g. Cushing's syndrome and acromegaly.
2. Any of the following significant laboratory abnormalities:
• Serum GAD-antibody positivity analyzed by the Central Laboratory.
• Clinically significant TSH outside of normal range at Screening analyzed by the Central Laboratory.
• Renal function indicating high risk metformin use, including serum creatinine concentrations (=1.5 mg/dL for males, =1.4 mg/dL for females) or other evidence of abnormal creatinine clearance.
• Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2 x upper limit of normal (ULN) at Screening, confirmed with repeat measure within one week.
• Total bilirubin > 2 times ULN and /or direct bilirubin greater than the ULN at Screening, confirmed by a repeat measurement within one week.
3. Known chronic liver disease of any aetiology.
4. History or current findings of active pulmonary disease (e.g. tuberculosis, fungal diseases) as evidenced by any of the following:
• History of positive PPD skin test result with positive chest x-ray/positive QFT-G test and no completion of treatment
• A positive PPD skin test plus a positive chest x-ray or positive QFT-G test (with or without positive chest x-ray ) during the screening period.
• History of a positive QFT-G test and no completion of treatment.
• History of a positive AFB sputum sample and no completion of treatment.
• Requirement for administration of antibiotics against latent tuberculosis (e.g., isoniazide). Courses of antibiotic therapy started prior to entering the study should not be prematurely terminated to allow inclusion into the study.
5. One of the risk factors for TB such as:
• History of any of the following: residence in a congregate setting (e.g. jail or prison, homeless shelter, or chronic care facility), substance abuse (e.g. injection or non-injection); health-care workers with unprotected exposure to patients who are at high risk of TB or patients with TB disease before the identification and correct airborne precautions of the patient, or
• Close contact (i.e. share the same air space in a household or other enclosed environment for a prolonged period (days or weeks, not minutes or hours)) with a person with active pulmonary TB disease.
6. Known presence or suspicion of active or recurrent bacterial, fungal or viral infection at the time of enrollment proven or suspected to be related to immunocompromisation, including patients with evidence of Human Immunodeficiency Virus (HIV) infection.
7. Known presence or suspicion of active or recurrent Hepatitis B and Hepatitis C infections (based on history and/or findings from the Central Lab).
8. Any surgical or underlying hepatic, hematologic, pulmonary, infectious, autoimmune or gastrointestinal conditions which in the opinion of the investigator immunocompromises the patient and/or places the patient at unacceptable risk for participation in immunodulatory therapy.
9. Any systemic treatment or local treatment of any immune modulating agent in doses with systemic effects. Topical , inhaled or local steriod use in doses that are not considered to cause systemic effects are permitted.
10. Live vaccinations within 3 months prior to the Randomization Visit or live vaccinations planned during the trial and up to three months following the last dose.
11. Stroke, myocardial infarction, acute coronary syndrome, revascularization proced

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Type II Diabetes Mellitus
MedDRA version: 9.1 Level: LLT Classification code 10012601 Term: Diabetes mellitus

Intervention(s)

Product Name: Canakinumab
Product Code: ACZ885
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: canakinumab
Current Sponsor code: ACZ885
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Powder for solution for injection
Route of administration of the placebo: Subcutaneous use

Product Name: Canakinumab
Product Code: ACZ885
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: canakinumab
Current Sponsor code: ACZ885
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Powder for solution for injection
Route of administration of the placebo: Subcutaneous use

Product Name: Canakinumab
Product Code: ACZ885
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: canakinumab
Current Sponsor code: ACZ885
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
Pharmaceutical form of the placebo: Powder for solution for injection
Route of administration of the placebo: Subcutaneous use

Product Name: Canakinumab
Product Code: ACZ885
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: canakinumab
Current Sponsor code: ACZ885
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Powder for solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: For Period II:
• To evaluate the effect of 4-month treatment of ACZ885 at doses 5 mg, 15 mg, 50 mg, and 150 mg vs. placebo on the following variables:
• Area under the curve (AUC) and peak values of C-peptide following meal test
• Area under the curve (AUC), 2-hour value and peak value of glucose and insulin following meal test
• Insulin secretion rate derived based on glucose and C-peptide following meal test
• Average and peak values based on 7-point glucose meter data

For Period IV:
• To evaluate the effect of long-term treatment of ACZ885 at the dose selected based on the efficacy and safety data from the 4-month treatment period vs. placebo on the following variables:
• Duration of insulin use and insulin dose
• Area under the curve (AUC) and peak values of C-peptide following meal test
• Area under the curve (AUC), 2-hour value and peak value of glucose and insulin following meal test
For detailed list see full protocol

Main Objective: For Period II
• To assess safety and tolerability of four doses of ACZ885 (5 mg, 15 mg, 50 mg, and 150 mg) vs. placebo as an add-on regimen over 4 months in patients with T2DM pre-treated and continuing on a stable dose of metformin = 1000 mg daily (or lower dose if required by local regulations).
• To assess the effect on HbA1c of four doses of ACZ885 (5 mg, 15 mg, 50 mg, and 150 mg) vs. placebo as an add-on regimen over 4 months in patients with T2DM pre-treated and continuing on a stable dose of metformin = 1000 mg daily (or lower dose if required by local regulations).
• To assess the anti-apoptotic effect of ACZ885 vs. placebo on the meal challenge derived dynamic phase secreted insulin per unit of glucose concentration in patients with T2SM who have been on study drug for 4 months, an interim analysis will be performed when 150 patients complete the Meal Challenge Test at Visit 8.
For Period III
see full protocol
For Period IV
see full protocol

Primary end point(s): The primary efficacy variable for the dose finding period (Period II) is the change from baseline in HbA1c at Month 4.

Secondary ID(s)

2009-009889-13-GB

CACZ885I2202